Target Information
| Target General Information | Top | |||||
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| Target ID |
T23714
(Former ID: TTDC00111)
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| Target Name |
B2 bradykinin receptor (BDKRB2)
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| Synonyms |
Bradykinin B2 receptor; BKR2; BK-2 receptor; BK B(2) receptor; B2R
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| Gene Name |
BDKRB2
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Innate/adaptive immunodeficiency [ICD-11: 4A00] | |||||
| Function |
It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. Receptor for bradykinin.
Click to Show/Hide
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MFSPWKISMFLSVREDSVPTTASFSADMLNVTLQGPTLNGTFAQSKCPQVEWLGWLNTIQ
PPFLWVLFVLATLENIFVLSVFCLHKSSCTVAEIYLGNLAAADLILACGLPFWAITISNN FDWLFGETLCRVVNAIISMNLYSSICFLMLVSIDRYLALVKTMSMGRMRGVRWAKLYSLV IWGCTLLLSSPMLVFRTMKEYSDEGHNVTACVISYPSLIWEVFTNMLLNVVGFLLPLSVI TFCTMQIMQVLRNNEMQKFKEIQTERRATVLVLVVLLLFIICWLPFQISTFLDTLHRLGI LSSCQDERIIDVITQIASFMAYSNSCLNPLVYVIVGKRFRKKSWEVYQGVCQKGGCRSEP IQMENSMGTLRTSISVERQIHKLQDWAGSRQ Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| ADReCS ID | BADD_A01105 ; BADD_A01502 ; BADD_A06794 | |||||
| HIT2.0 ID | T85J2J | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Icatibant | Drug Info | Approved | Hereditary angioedema | [2], [3], [4] | |
| Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
| 1 | Anatibant | Drug Info | Phase 2 | Traumatic brain injury | [5], [6] | |
| 2 | DELTIBANT | Drug Info | Phase 2 | Sepsis | [7] | |
| 3 | DM199 | Drug Info | Phase 2 | Ischemic stroke | [8], [9] | |
| 4 | Fasitibant chloride | Drug Info | Phase 2 | Osteoarthritis | [10] | |
| Discontinued Drug(s) | [+] 6 Discontinued Drugs | + | ||||
| 1 | Labradimil | Drug Info | Discontinued in Phase 2 | Brain cancer | [11], [12] | |
| 2 | NPC-567 | Drug Info | Discontinued in Phase 2 | Rhinitis | [13], [14] | |
| 3 | CP-0597 | Drug Info | Terminated | Asthma | [15] | |
| 4 | FR-172357 | Drug Info | Terminated | Inflammation | [16] | |
| 5 | JSM-10292 | Drug Info | Terminated | Pain | [17] | |
| 6 | NPC-17731 | Drug Info | Terminated | Asthma | [18], [19] | |
| Mode of Action | [+] 5 Modes of Action | + | ||||
| Antagonist | [+] 16 Antagonist drugs | + | ||||
| 1 | Icatibant | Drug Info | [1], [20], [21] | |||
| 2 | Anatibant | Drug Info | [22], [23] | |||
| 3 | Fasitibant chloride | Drug Info | [25] | |||
| 4 | CP-0597 | Drug Info | [30] | |||
| 5 | FR-172357 | Drug Info | [31] | |||
| 6 | JSM-10292 | Drug Info | [33] | |||
| 7 | NPC-17731 | Drug Info | [34] | |||
| 8 | bradyzide | Drug Info | [36] | |||
| 9 | chroman 28 | Drug Info | [38] | |||
| 10 | FR167344 | Drug Info | [39] | |||
| 11 | JMV1431 | Drug Info | [26] | |||
| 12 | NPC-349 | Drug Info | [42] | |||
| 13 | PMID12723943C12 | Drug Info | [45] | |||
| 14 | PMID12812482C11 | Drug Info | [46] | |||
| 15 | PS020990 | Drug Info | [47] | |||
| 16 | WIN 64338 | Drug Info | [50] | |||
| Modulator | [+] 3 Modulator drugs | + | ||||
| 1 | DELTIBANT | Drug Info | [7] | |||
| 2 | Breceptin | Drug Info | [37] | |||
| 3 | LF-160335 | Drug Info | [43] | |||
| Activator | [+] 1 Activator drugs | + | ||||
| 1 | DM199 | Drug Info | [24] | |||
| Inhibitor | [+] 11 Inhibitor drugs | + | ||||
| 1 | BRADYKININ | Drug Info | [26] | |||
| 2 | NPC-567 | Drug Info | [29] | |||
| 3 | FR-173657 | Drug Info | [32] | |||
| 4 | (D)Arg-Arg-Pro-Hyp-Gly-Phe-Ser-(d)Phe-Phe-Arg | Drug Info | [35] | |||
| 5 | (D)Arg-Arg-Pro-Hyp-Gly-Thi-Cys-(D)Phe-Phe-Cys-Arg | Drug Info | [35] | |||
| 6 | (D)Arg-Arg-Pro-Hyp-Gly-Thi-Ser-(D)Tic-Aoc-Arg | Drug Info | [35] | |||
| 7 | (D)Arg-Arg-Pro-Hyp-Gly-Thi-Ser-(D)Tic-Tic-Arg | Drug Info | [35] | |||
| 8 | H-DArg-Arg-Pro-Hyp-Gly-Igl-Ser-D-BT-OH(JMV1638) | Drug Info | [26] | |||
| 9 | H-Lys-Arg-Pro-Hyp-Gly-Igl-Ser-D-BT-OH(JMV1645) | Drug Info | [26] | |||
| 10 | H-Lys-Arg-Pro-Hyp-Gly-Thi-Ser-D-BT-OH(JMV1669) | Drug Info | [26] | |||
| 11 | Quinapril analogue | Drug Info | [48] | |||
| Agonist | [+] 9 Agonist drugs | + | ||||
| 1 | Labradimil | Drug Info | [27], [28] | |||
| 2 | FR190997 | Drug Info | [40] | |||
| 3 | FR191413 | Drug Info | [41] | |||
| 4 | kallidin | Drug Info | [42] | |||
| 5 | Met-Lys-bradykinin | Drug Info | [44] | |||
| 6 | T-kinin | Drug Info | [49] | |||
| 7 | [des-Arg9]bradykinin | Drug Info | [51] | |||
| 8 | [Leu8,des-Arg9]bradykinin | Drug Info | [52] | |||
| 9 | [Sar,D-Phe8,des-Arg9]bradykinin | Drug Info | [49] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Bradykinin receptor antagonists--a review of the patent literature 2005-2008. Expert Opin Ther Pat. 2009 Jul;19(7):919-41. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 667). | |||||
| REF 3 | 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4. | |||||
| REF 4 | Icatibant , the bradykinin B2 receptor antagonist with target to the interconnected kinin systems. Expert Opin Pharmacother. 2012 Oct;13(15):2233-47. | |||||
| REF 5 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 679). | |||||
| REF 6 | Emerging treatments for traumatic brain injury. Expert Opin Emerg Drugs. 2009 Mar;14(1):67-84. | |||||
| REF 7 | CP-0127, a novel potent bradykinin antagonist, increases survival in rat and rabbit models of endotoxin shock. Agents Actions Suppl. 1992;38 ( Pt 3):413-20. | |||||
| REF 8 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 9 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 10 | ClinicalTrials.gov (NCT01091116) A Locally Injected Bradykinin Antagonist for TReatment of OSteoarthritiS. U.S. National Institutes of Health. | |||||
| REF 11 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 672). | |||||
| REF 12 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006912) | |||||
| REF 13 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 676). | |||||
| REF 14 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002385) | |||||
| REF 15 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008984) | |||||
| REF 16 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008533) | |||||
| REF 17 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024715) | |||||
| REF 18 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 657). | |||||
| REF 19 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007977) | |||||
| REF 20 | Pharmacological characterization of the bradykinin B2 receptor antagonist MEN16132 in rat in vitro bioassays. Eur J Pharmacol. 2009 Aug 1;615(1-3):10-6. | |||||
| REF 21 | Bradykinin in the heart: friend or foe Circulation. 1999 Dec 7;100(23):2305-7. | |||||
| REF 22 | Inhibition of bradykinin B2 receptors before, not after onset of experimental subarachnoid hemorrhage prevents brain edema formation and improves functional outcome. Crit Care Med. 2009 Jul;37(7):2228-34. | |||||
| REF 23 | Anatibant, a selective non-peptide bradykinin B2 receptor antagonist, reduces intracranial hypertension and histopathological damage after experime... Neurosci Lett. 2009 Apr 24;454(2):115-7. | |||||
| REF 24 | Pharmacological effects of recombinant human tissue kallikrein on bradykinin B2 receptors. Pharmacol Res Perspect. 2015 Mar;3(2):e00119. | |||||
| REF 25 | Fasitibant chloride, a kinin B receptor antagonist, and dexamethasone interact to inhibit carrageenan-induced inflammatory arthritis in rats. Br J Pharmacol. 2012 Jun;166(4):1403-10. | |||||
| REF 26 | Synthesis and biological evaluation of bradykinin B(1)/B(2) and selective B(1) receptor antagonists. J Med Chem. 2000 Jun 15;43(12):2382-6. | |||||
| REF 27 | Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life. J Transl Med. 2009 May 13;7:33. | |||||
| REF 28 | Bradykinin receptor agonist facilitates low-dose cyclosporine-A protection against 6-hydroxydopamine neurotoxicity. Brain Res. 2002 Nov 29;956(2):211-20. | |||||
| REF 29 | cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain... J Med Chem. 2008 Nov 27;51(22):7094-8. | |||||
| REF 30 | CP-0597, a selective bradykinin B2 receptor antagonist, inhibits brain injury in a rat model of reversible middle cerebral artery occlusion. Stroke. 1997 Jul;28(7):1430-6. | |||||
| REF 31 | Characterization of FR 172357, a new non-peptide bradykinin B(2) receptor antagonist, in human, pig and rabbit preparations. Eur J Pharmacol. 1999 Dec 10;386(1):25-31. | |||||
| REF 32 | Novel small molecule bradykinin B2 receptor antagonists. J Med Chem. 2009 Jul 23;52(14):4370-9. | |||||
| REF 33 | Binding characteristics of [3H]-JSM10292: a new cell membrane-permeant non-peptide bradykinin B2 receptor antagonist. Br J Pharmacol. 2012 Oct;167(4):839-53. | |||||
| REF 34 | Antinociceptive profile of the pseudopeptide B2 bradykinin receptor antagonist NPC 18688 in mice. Br J Pharmacol. 1996 Feb;117(3):552-558. | |||||
| REF 35 | Design and conformational analysis of several highly potent bradykinin receptor antagonists. J Med Chem. 1991 Mar;34(3):1230-3. | |||||
| REF 36 | Bradyzide, a potent non-peptide B(2) bradykinin receptor antagonist with long-lasting oral activity in animal models of inflammatory hyperalgesia. Br J Pharmacol. 2000 Jan;129(1):77-86. | |||||
| REF 37 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 42). | |||||
| REF 38 | Identification of a nonpeptidic and conformationally restricted bradykinin B1 receptor antagonist with anti-inflammatory activity. J Med Chem. 2007 Feb 22;50(4):607-10. | |||||
| REF 39 | Novel subtype-selective nonpeptide bradykinin receptor antagonists FR167344 and FR173657. Mol Pharmacol. 1997 Feb;51(2):171-6. | |||||
| REF 40 | Nonpeptide mimic of bradykinin with long-acting properties at the bradykinin B2 receptor. Mol Pharmacol. 1997 Jul;52(1):16-20. | |||||
| REF 41 | Discovery of the first non-peptide full agonists for the human bradykinin B(2) receptor incorporating 4-(2-picolyloxy)quinoline and 1-(2-picolyl)benzimidazole frameworks. J Med Chem. 2004 May 20;47(11):2853-63. | |||||
| REF 42 | Differential pharmacology of cloned human and mouse B2 bradykinin receptors. Mol Pharmacol. 1994 Jan;45(1):1-8. | |||||
| REF 43 | The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954. | |||||
| REF 44 | Expression cloning of a human B1 bradykinin receptor. J Biol Chem. 1994 Aug 26;269(34):21583-6. | |||||
| REF 45 | Benzodiazepines as potent and selective bradykinin B1 antagonists. J Med Chem. 2003 May 8;46(10):1803-6. | |||||
| REF 46 | Discovery of a potent, non-peptide bradykinin B1 receptor antagonist. J Am Chem Soc. 2003 Jun 25;125(25):7516-7. | |||||
| REF 47 | Small molecule antagonists of the bradykinin B1 receptor. Immunopharmacology. 1999 Sep;43(2-3):169-77. | |||||
| REF 48 | Ace inhibitors as a template for the design of bradykinin B2 receptor antagonists, Bioorg. Med. Chem. Lett. 5(4):367-370 (1995). | |||||
| REF 49 | Molecular characterisation of cloned bradykinin B1 receptors from rat and human. Eur J Pharmacol. 1999 Jun 25;374(3):423-33. | |||||
| REF 50 | Design of potent non-peptide competitive antagonists of the human bradykinin B2 receptor. J Med Chem. 1993 Aug 20;36(17):2583-4. | |||||
| REF 51 | Stable expression of human kinin B1 receptor in 293 cells: pharmacological and functional characterization. Br J Pharmacol. 1997 Sep;122(2):393-9. | |||||
| REF 52 | Partial agonists and full antagonists at the human and murine bradykinin B1 receptors. Can J Physiol Pharmacol. 1997 Jun;75(6):735-40. | |||||
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